TREX1 is a broadly expressed 3’ to 5’ exonuclease that acts on single-stranded DNA (ssDNA) to negatively regulate the interferon-stimulatory DNA (ISD) response. In humans, there are three TREX1 isoforms generated through alternative splicing with predicted molecular weights of 32, 33, and 39 kDa. The transcript for the 33 kDa isoform is the most abundant. Mice deficient in TREX1 accumulate intracellular ssDNA, which triggers the ISD response and eventually lethal autoimmunity. Mutations in TREX1 are associated with autoimmune diseases including Aicardi-Goutieres syndrome and systemic lupus erythematosus. In addition, TREX1 prevents the cell-intrinsic innate immune response to human immunodeficiency virus (HIV) by digesting excess HIV DNA that would normally trigger induction of type I interferon.
